The goal of this research project is to study physiological and pathological factors which may influence brain metabolism and the kinetics of metabolite transport at the blood-capillary endothelial cell interface (blood-brain barrier) and relate the findings to the corresponding condition in vivo. The isolated perfused canine brain preparation is used to study unidirectional transport at the blood-capillary endothelial cell interface using an indicator dilution method with 22Na as the intravascular reference and 3H labeled compounds as test molecules. Cerebral glucose transport kinetics will be characterized in terms of their pH, temperature and blood flow rate dependence. Glucose indicator dilution data derived under a variety of physiological and pathological conditions will be fitted to a compartmental model for the calculation of glucose fractional utilization, forward:reverse glucose flux, metabolic rate for glucose, relative tissue-free glucose space, brain-free glucose turnover time and tissue glucose concentration. The blood-brain barrier will be modified by inducing bacterial meningitis in the animal prior to surgery and studying glucose transport kinetics following brain isolations. Unidirectional glucose flux, blood-brain barrier integrity, cerebral O2 uptake, regional blood flow (microsphere method), metabolic control of glycolysis and high energy phosphate content will be determined during and following 30 minute periods of brain perfusion with blood which has either a PO2 of 20mm Hg, 30mm Hg or is 50% saturated with O2 at 15mm Hg rather than 30mm Hg as a result of hemoglobin modification with cyanate.